Nivolumab VERSUS Cabozantinib as Second-Line Therapy in Patients With Advanced Renal Cell Carcinoma: A Real-World Comparison

•Herein, we investigated the real-world efficacy of nivolumab and cabozantinib as second-line therapy in a cohort of 343 patients in a real-world setting.•We observed an advantage for nivolumab in terms of overall survival (OS) in almost all the subgroups analyzed, without reporting a statistically significant difference, except for patients with bone metastases or progressed during first-line sunitinib, characterized by longer survival with cabozantinib.•Median progression-free survival (PFS) was higher with cabozantinib in the majority of the subgroup analyses and resulted statistically significantly longer in male patients, in clear cell renal cell carcinoma (ccRCC) histology and in the good risk subgroup.•According to our results, nivolumab and cabozantinib were active in mRCC patients, showing distinct results when stratified into clinico-pathological features. Tyrosine-kinase inhibitors (TKIs) still represent a first-line option for selected patients with metastatic Renal Cell Carcinoma (mRCC). We aimed to compare the real-world efficacy of nivolumab or cabozantinib as second-line therapy in specific mRCC subpopulations. We retrospectively collected data from 11 centers from Italy, Spain and US. Overall Survival (OS) and Progression-Free Survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 343 patients with mRCC, 123 (36%) treated with cabozantinib and 220 (64%) with nivolumab. The median OS resulted longer, but not statistically significant, with nivolumab in patients aged >70 years (21.4 vs. 15.4 months, P = .746), treated with first-line pazopanib (26.8 vs. 11.6 months, P = .450), or with good (47.0 vs. 15.5 months, P = .285) or intermediate-risk criteria (14.4 vs. 11.0 months, P = .357), while it was longer, but even not statistically significant, for cabozantinib in patients who received previous sunitinib (25.7 vs. 21.7 months, P = .638) or with bone metastases (28.4 vs. 24.4 months, P = .871). The median PFS was significantly longer with cabozantinib in patients with clear cell histology (7.8 vs. 5.4 months, P = .026) and in patients with good risk features (12.3 vs. 5.7 months, P = .022). Nivolumab and cabozantinib resulted active in mRCC patients, showing distinct results when stratified into clinico-pathological features. Tyrosine-kinase inhibitors still represent a first-line option for selected patients with metastatic Renal Cell Carcinoma